Polyethylene glycol–polylactic acid nanoparticles modified with cysteine–arginine–glutamic acid–lysine–alanine fibrin-homing peptide for glioblastoma therapy by enhanced retention effect
Junzhu Wu,1,2,* Jingjing Zhao,1,3,* Bo Zhang,1 Yong Qian,1 Huile Gao,1 Yuan Yu,1 Yan Wei,1 Zhi Yang,1 Xinguo Jiang,1 Zhiqing Pang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 2School of Pharmacy, Dali U...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2014
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/10fa0f5d8a5a40bab1d5d5d3c13e4b16 |
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| Sumario: | Junzhu Wu,1,2,* Jingjing Zhao,1,3,* Bo Zhang,1 Yong Qian,1 Huile Gao,1 Yuan Yu,1 Yan Wei,1 Zhi Yang,1 Xinguo Jiang,1 Zhiqing Pang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 2School of Pharmacy, Dali University, Xiaguan, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: For a nanoparticulate drug-delivery system, crucial challenges in brain-glioblastoma therapy are its poor penetration and retention in the glioblastoma parenchyma. As a prevailing component in the extracellular matrix of many solid tumors, fibrin plays a critical role in the maintenance of glioblastoma morphology and glioblastoma cell differentiation and proliferation. We developed a new drug-delivery system by conjugating polyethylene glycol–polylactic acid nanoparticles (NPs) with cysteine–arginine–glutamic acid–lysine–alanine (CREKA; TNPs), a peptide with special affinity for fibrin, to mediate glioblastoma-homing and prolong NP retention at the tumor site. In vitro binding tests indicated that CREKA significantly enhanced specific binding of NPs with fibrin. In vivo fluorescence imaging of glioblastoma-bearing nude mice, ex vivo brain imaging, and glioblastoma distribution demonstrated that TNPs had higher accumulation and longer retention in the glioblastoma site over unmodified NPs. Furthermore, pharmacodynamic results showed that paclitaxel-loaded TNPs significantly prolonged the median survival time of intracranial U87 glioblastoma-bearing nude mice compared with controls, Taxol, and NPs. These findings suggested that TNPs were able to target the glioblastoma and enhance retention, which is a valuable strategy for tumor therapy. Keywords: CREKA peptide, nanoparticles, retention effect, paclitaxel, glioblastoma |
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